Pancreatic cancer hijacks metabolism switch to help it spread

Researchers at the Garvan Institute of Medical Research say they have uncovered how pancreatic cancer hijacks a crucial metabolism ‘switch’ to help it spread, revealing a potential new treatment strategy for this highly aggressive disease.

Pancreatic cancer is one of the deadliest forms of cancer, with an average five-year survival rate of just 13%. With metastasis (or spread) a major factor in the lethality of the disease, developing treatments that can prevent cancer from spreading is critically important. The Garvan study, published in the journal Science Advances, has now identified the signalling molecule neuropeptide Y (NPY) as a key driver of pancreatic cancer metastasis.

“Our research shows that pancreatic cancer hijacks a molecule known for regulating physiological processes, such as food intake and energy balance, and uses it to promote its own spread,” said first author Dr Cecilia Chambers, who completed the study as a PhD researcher at Garvan. The study is the first time the role of NPY has been investigated in pancreatic cancer metastasis, building on previous research that linked the molecule to cancer progression in breast, prostate and neuroblastoma cancers.

“We found NPY to be significantly higher in pancreatic cancer cells compared to normal tissue,” noted Dr David Herrmann, senior author of the study and Group Leader at Garvan.

When the researchers blocked NPY’s function in mouse models, they found they could substantially reduce the spread of pancreatic cancer to the liver — the most common site of metastasis in patients. This suggests NPY is a promising target to investigate further for pancreatic cancer, Herrmann said.

“Surprisingly, in addition to the anti-metastatic effect we observed, blocking NPY also helped reduce the loss of muscle and fat tissue mass — known as cachexia — that often accompanies cancer progression,” he added. “This additional benefit to maintain muscle and fat tissue could be crucial for patients to tolerate chemotherapy and other treatments.”

The team’s findings could pave the way for more targeted treatments, according to Professor Paul Timpson, Head of the Invasion and Metastasis Lab at Garvan. “We found particularly high levels of NPY in highly aggressive and metastatic pancreatic cancers,” he said. “This suggests that blocking NPY could be an effective personalised treatment for this subset of patients, as well as those who experience severe weight loss due to cancer.”

Following their findings, the researchers developed an antibody designed to neutralise NPY’s effect in cancer, which they are now testing in mouse models and in tissues donated by pancreatic cancer patients. The research team is now working to optimise how their new strategy could be combined with existing treatments.

“One of our next steps is to refine how we use this approach in combination with chemotherapy,” Herrmann said. “There’s growing evidence that timing is critical; thus, determining whether NPY inhibition is most effective when introduced before or after chemotherapy is important. Understanding this will be key to translating our findings into clinical trials, and ultimately to improve the outcomes of this disease.”

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